摘要
Objective： To investigate the synergistic effects of carnosic acid （CA） with arsenic trioxide （As203） on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects. Methods： HL-60 cellular proliferation was measured by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTF） analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl-2-associated agonist of cell death （BAD）, p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten （PTEN）, Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction （RT-PCR） analysis. Results： CA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, subsequently inhibited phosphorylation of BAD, reactivated caspase-9, and elevated levels of p27. CA also augmented these effects of As203. Conclusion： CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway.
Objective： To investigate the synergistic effects of carnosic acid （CA） with arsenic trioxide （As203） on proliferation and apoptosis in HL-60 human myeloid leukemia cells, and the major cellular signaling pathway involved in these effects. Methods： HL-60 cellular proliferation was measured by 3-（4,5-dimethylthiazol-2-yl）- 2,5-diphenyltetrazolium bromide （MTF） analysis. Cell cycle distribution and apoptosis were monitored by flow cytometry. The activation of casepase-9, Bcl-2-associated agonist of cell death （BAD）, p-BAD, p27, phosphatase and tensin homolog deleted on chromosome ten （PTEN）, Akt, p-Akt was assessed by Western blot analysis. The expression of PTEN mRNA was tested by reverse transcription polymerase chain reaction （RT-PCR） analysis. Results： CA reduced HL-60 cell viability in a dose- and time-dependent manner, and induced G1 arrest and apoptosis. Moreover, CA upregulated PTEN expression, blocked the Akt signaling pathway, subsequently inhibited phosphorylation of BAD, reactivated caspase-9, and elevated levels of p27. CA also augmented these effects of As203. Conclusion： CA might be a novel candidate of the combination therapy for leukemia treatment; these effects were apparently associated with the modulation of PTEN/Akt signaling pathway.
基金
Supported by the National Natural Science Foundation of China (No.81102710)
